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Variability of drug self-administration in rats
Leigh V Panlilio1, Jonathan L Katz, Roy W Pickens
1Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov
Rationale:
Although temporal patterns of drug self-administration in animals are known to be highly regular, this regularity has rarely been quantified or systematically compared across reinforcers.
Objectives:
Over a range of unit doses, this study assessed: (1) the within-subject variability of inter-infusion intervals (latencies); (2) the estimated whole-body drug level at the time of self-infusion; (3) the within-subject variability of these drug levels; and (4) the statistical dependence between successive latencies, to determine whether regularity is maintained by compensatory, moment-to-moment adjustment of latencies.
Methods:
Rats were trained with cocaine (10-1000 microg/kg per infusion, IV), remifentanil (an ultra-short acting opioid; 0.25-32 microg/kg per infusion, IV), or food (20-180 mg/delivery).
Results:
Within subjects, latencies were most consistent from infusion to infusion at unit doses on the descending limb of the dose-response curve. However, the drug level at the time an infusion was initiated was actually least consistent at these doses. Sequential latencies showed only a weak autocorrelation for both drugs.
Conclusion:
These results suggest that highly consistent response patterns are not simply a product of precise titration of drug levels. The weak autocorrelation between sequential latencies suggests that temporal regularity of responding is not maintained through compensatory adjustments of post-infusion pauses.